Acid-evoked quantal catecholamine secretion from rat phaeochromocytoma cells and its interaction with hypoxia-evoked secretion

1. Amperometric recordings using polarized carbon fibre microelectrodes wer e used to detect exocytosis of catecholamines from rat phaeochromocytoma (P C12) cells in response to a reduction in pH(o). 2. Exocytosis was detected at pH(o) levels of between 7.2 and 6.8. This was probably due to intracellular acidification, since acid-evoked secretion w as enhanced by the Na+-H+ exchange blocker ethylisopropylamiloride (30 mu M ), and was mimicked by sodium propionate (10 mM), which causes selective in tracellular acidosis. 3. Acid-evoked exocytosis was abolished by removal of Ca-o(2+) or applicati on of 200 mu M Cd2+. It was unaffected by nifedipine, but significantly red uced by either omega-conotoxin GVIA (1 mu M) or omega-agatoxin GIVA (200 nM ). The two toxins applied together almost completely abolished (> 97%) acid -evoked secretion. 4. Hypoxia-evoked catecholamine release was potentiated under acidic condit ions and suppressed under alkaline conditions in a manner which indicated a greater than additive interaction of these two stimuli. 5. Our results indicate that, like carotid body arterial chemoreceptors, PC 12 cells represent model chemoreceptor cells for both hypoxia and acidity a nd that the release of catecholamines in response to these physiological st imuli is dependent on Ca2+ influx through voltage-gated N- and P/Q-type Ca2 + channels.